Novel pathophysiology underlying cardiac conduction defect due to mutations of gap junction genes

• Project/Area Number: 18K19550
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: National Cardiovascular Center Research Institute (2019-2020); Nagasaki University (2018)
• Principal Investigator: Makita Naomasa 国立研究開発法人国立循環器病研究センター, 研究所, 副所長 (00312356)
• Co-Investigator(Kenkyū-buntansha): 西井 明子 (関明子) 東京女子医科大学, 医学部, 准教授 (80408608) ; 柴田 恭明 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (80253673) ; 本荘 晴朗 名古屋大学, 環境医学研究所, 准教授 (70262912)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ギャップ結合 / コネキシン40 / コネキシン45 / 心臓伝導障害 / ノックインマウス / CRISPR/Cas9 / ゲノム編集 / 胎生致死 / コネキシン４５ / 歯骨形成異常 / Crispr/Cas9ゲノム編集 / Crispr/cas9ゲノム編集 / コネキシン / 進行性心臓伝導障害 / 歯骨格異常 / 光学マッピング

Outline of Final Research Achievements

In contrast to patients with connexin mutations,Cx40-Q58L heterozygous knock-in mice showed no conduction disturbance. We also established another Cx40-Q58L mice with Cx30.2 knock-out, but we failed to restore the frozen embryos probably due to some technical problems. For Cx45-Q58L, we tried several methods including CRISPR/Cas9 and iGONAD, but we failed to establish the Cx45-R57H knock-in mice, probably because perturbations of the Cx45 protein during the embryonic stage may not be compatible with life .

Academic Significance and Societal Importance of the Research Achievements

Cx40変異, C45変異はともに伝導障害患者で同定された変異だが、Cx40変異のヘテロノックインマウスは心臓伝導障害を示さず、Cx45変異のヘテロヘテロノックインマウスは逆に、おそらく胎生致死のために樹立されなかった。これは心臓コネキシンサブユニットの分布や機能に明らかな種差があることを示唆する。将来的に心臓コネキシン病の動物モデルを作成する際には、マウス以外の動物を考慮する必要がある。

Research Products

• [Journal Article] Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls (2020)
  • Author(s): 2.Walsh R, Lahrouchi N, Tadros R, Kyndt F, Glinge C, Postema PG, et al.
  • Journal Title: Genetics in Medicine Volume: 23 Issue: 1 Pages: 47-58
  • DOI: 10.1038/s41436-020-00946-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SCN5A Mutation Type and a Genetic Risk Score Associate Variably With Brugada Syndrome Phenotype in SCN5A Families (2020)
  • Author(s): 3.Wijeyeratne YD, Tanck MW, Mizusawa Y, Batchvarov V, Barc J, Crotti L, et al.
  • Journal Title: Circulation: Genomic and Precision Medicine Volume: 13 Issue: 6
  • DOI: 10.1161/circgen.120.002911
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cardiac Emerinopathy (2020)
  • Author(s): Ishikawa Taisuke、Ichida Fukiko、Makita Naomasa et al
  • Journal Title: Circulation: Arrhythmia and Electrophysiology Volume: 13 Issue: 10 Pages: 1165-1174
  • DOI: 10.1161/circep.120.008712
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome (2020)
  • Author(s): Lahrouchi N, Tadros R, Crotti L, Makiyama T et al.
  • Journal Title: Circulation Volume: 142 Issue: 4 Pages: 324-338
  • DOI: 10.1161/circulationaha.120.045956
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transethnic genome-wide association study provides insights in the genetic architecture and heritability of long QT syndrome (2020)
  • Author(s): Lahrouchi N., Ishikawa T., Makita N., et al.
  • Journal Title: Circulation Volume: -
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway (2020)
  • Author(s): Miyao N., Hata Y., Izumi H., Nagaoka R., Oku Y., Takasaki I., Ishikawa T., Takarada S., Okabe M., Nakaoka H., Ibuki K., Ozawa S., Yoshida T., Hasegawa H., Makita N., Nishida N., Mori H., Ichida F., Hirono K.
  • Journal Title: PLOS ONE Volume: 15 Issue: 4 Pages: 0227393-0227393
  • DOI: 10.1371/journal.pone.0227393
  • Peer Reviewed / Open Access
• [Journal Article] Desmin‐related myopathy characterized by non‐compaction cardiomyopathy, cardiac conduction defect, and coronary artery dissection (2020)
  • Author(s): Tamiya R., Saito Y., Fukamachi D., Nagashima K., Aizawa Y., Ohkubo K., Hatta T., Sezai A., Tanaka M, Ishikawa T., Makita N., Sumitomo N., Okumura Y.
  • Journal Title: ESC Heart Failure Volume: - Issue: 3 Pages: 1338-1343
  • DOI: 10.1002/ehf2.12667
  • Peer Reviewed / Open Access
• [Journal Article] Identification of transmembrane protein 168 mutation in familial Brugada syndrome. (2020)
  • Author(s): Shimizu A, Zankov DP, Sato A, Komeno M, Toyoda F, Yamazaki S, Makita T, Noda T, Ikawa M, Asano Y, Miyashita Y, Takashima S, Morita H, Ishikawa T, Makita N, Hitosugi M, Matsuura H, Ohno S, Horie M, Ogita H.
  • Journal Title: FASEB Journal Volume: 34 Issue: 5 Pages: 6399-6417
  • DOI: 10.1096/fj.201902991r
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pathological Features of Lamin Cardiomyopathy (2020)
  • Author(s): Kawano H., Ishimatsu T., Ishijima I., Hayashi T., Ishikawa T., Makita N., Maemura K.
  • Journal Title: Circulation Journal Volume: -
  • NAID: 130007864268
  • Peer Reviewed / Open Access
• [Journal Article] Brugada症候群の遺伝的背景 (2020)
  • Author(s): 蒔田直昌
  • Journal Title: 別冊・医学のあゆみ 遺伝性心血管疾患のすべて Volume: - Pages: 87-90
• [Journal Article] Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry (2019)
  • Author(s): Crotti Lia、Spazzolini Carla、Tester David J、Ohno Seiko、Ackerman Michael J、Schwartz Peter J, et al.
  • Journal Title: European Heart Journal Volume: 40 Issue: 35 Pages: 2964-2975
  • DOI: 10.1093/eurheartj/ehz311
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 遺伝性不整脈のPrecision medicine (2019)
  • Author(s): 石川泰輔, 蒔田直昌
  • Journal Title: 週間 医学のあゆみ Volume: 272 Pages: 1279-1283
• [Journal Article] 遺伝性不整脈の遺伝子診断：有効性と限界 (2019)
  • Author(s): 石川泰輔, 蒔田直昌
  • Journal Title: 循環器病研究の進歩 Volume: 40 Pages: 58-66
  • Peer Reviewed
• [Journal Article] Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients (2019)
  • Author(s): Shimizu Wataru、Makimoto Hisaki、Yamagata Kenichiro、Kamakura Tsukasa、Wada Mitsuru、Miyamoto Koji、Inoue-Yamada Yuko、Okamura Hideo、Ishibashi Kohei、Noda Takashi、Nagase Satoshi、Miyazaki Aya、Sakaguchi Heima、Shiraishi Isao、Makiyama Takeru、Ohno Seiko、Itoh Hideki、et al
  • Journal Title: JAMA Cardiology Volume: in press Issue: 3 Pages: 246-254
  • DOI: 10.1001/jamacardio.2018.4925
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical Manifestations and Long-Term Mortality in <i>Lamin A/C</i> Mutation Carriers From a Japanese Multicenter Registry (2018)
  • Author(s): 14.Nakajima K, Aiba T, Makiyama T, Nishiuchi S, Ohno S, Kato K, Yamamoto Y, Doi T, Shizuta S, Onoue K, Yagihara N, Ishikawa T, Watanabe I, Kawakami H, Oginosawa Y, Murakoshi N, Nogami A, Aonuma K, Saito Y, Kimura T, Yasuda S, Makita N, Shimizu W, Horie M, Kusano K.
  • Journal Title: Circulation Journal Volume: 82 Issue: 11 Pages: 2707-2714
  • DOI: 10.1253/circj.CJ-18-0339
  • NAID: 40021697176
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2018-10-25
  • Peer Reviewed / Open Access
• [Journal Article] HCN4 Gene Polymorphisms Are Associated With Occurrence of Tachycardia-Induced Cardiomyopathy in Patients With Atrial Fibrillation (2018)
  • Author(s): Nakano Yukiko、Ochi Hidenori、Sairaku Akinori、Onohara Yuko、Tokuyama Takehito、Motoda Chikaaki、Matsumura Hiroya、Tomomori Shunsuke、Amioka Michitaka、Hironobe Naoya、Ohkubo Yousaku、Okamura Shou、Makita Naomasa、Yoshida Yukihiko、Chayama Kazuaki、Kihara Yasuki
  • Journal Title: Circulation: Genomic and Precision Medicine Volume: 11 Issue: 7 Pages: 1-7
  • DOI: 10.1161/circgen.117.001980
  • Peer Reviewed
• [Journal Article] HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node (2018)
  • Author(s): Kozasa Yuko、Nakashima Noriyuki、Ito Masayuki、Ishikawa Taisuke、Kimoto Hiroki、Ushijima Kazuo、Makita Naomasa、Takano Makoto
  • Journal Title: The Journal of Physiology Volume: 596 Issue: 5 Pages: 809-825
  • DOI: 10.1113/jp275303
  • Peer Reviewed / Open Access
• [Journal Article] Lack of genotype-phenotype correlation in Brugada Syndrome and Sudden Arrhythmic Death Syndrome families with reported pathogenic SCN1B variants (2018)
  • Author(s): Gray B., Hasdemir C., Ingles J., Aiba T., Makita N., Probst V., Wilde A. A. M., Newbury-Ecob R., Sheppard M. N., Semsarian C., Sy R. W., Behr E. R.
  • Journal Title: Heart Rhythm Volume: 15 Issue: 7 Pages: 1051-1057
  • DOI: 10.1016/j.hrthm.2018.03.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interaction of Phase Singularities on Spiral Wave Tail: Reconsideration of Caputuring Excitable Gap. (2018)
  • Author(s): Tomii N, Yamazaki M, Arafune T, Kamiya K, Nakazawa K, Honjo H, Shibata N, Sakuma I.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: in press Issue: 2 Pages: 318-326
  • DOI: 10.1152/ajpheart.00558.2017
  • Peer Reviewed
• [Presentation] Genetic Risks of Sudden Death in Brugada Syndrome (2020)
  • Author(s): Makita N.
  • Organizer: 第84回日本循環器学会学術集会
  • Int'l Joint Research / Invited
• [Presentation] Cardiac Emerinopathy, Novel Non-syndromic X-linked Left Ventricular Noncompaction Associated with Progressive Atrial Conduction Disturbance (2020)
  • Author(s): Ishikawa T, Aiba T, Ohno S, Yoshiura K, Makita N et al.
  • Organizer: 第84回日本循環器学会学術集会
  • Int'l Joint Research
• [Presentation] Single Cell Electrophysiological Analysis of iPS Cell-Derived Cardiomyocytes Generated from Long-QT Syndrome Patients Carrying a CALM2 Mutation Using a Membrane Potential Imaging System (2019)
  • Author(s): Yamamoto Y., Makiyama T., Wuriyanghai Y., Kohjitani H., Hirose S., Gao J., Kashiwa A., Huang H., Ishikawa T., Ohno S., Chonabayashi K., Suda K., Yoshida Y., Horie M., Makita N., Kimura T.
  • Organizer: 第66回日本不整脈心電学会
• [Presentation] Comprehensive Analyses Using Functional Evaluation and Whole-exome Sequencings to Decipher the Genetic predispositions for Sudden Death in Brugada Syndrome (2019)
  • Author(s): Makita N., Ishikawa T., Japanese Brugada Exome Consortium Investigators
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Genetic of cardiac conduction disturbance (2019)
  • Author(s): Makita N.
  • Organizer: 12th Asia Pacific heart Rhythm Society Scientific Session
  • Int'l Joint Research / Invited
• [Presentation] A case report of juvenile onset familial atrial fibrillation due to genetic defect (2019)
  • Author(s): Kumanomidou J., Makita N.
  • Organizer: 12th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research
• [Presentation] Modeling Overlap Syndrome of Long QT and Brugada Syndrome Associated with Induced Pluripotent Stem Cells (2019)
  • Author(s): Kashiwa A., Makiyama T., Kohjitani H., Wuriyanghai Y., Yamamoto Y., Jungshan G., Huang H., Ishikawa T., Ohno S., Toyoda F., Sato S., Horie M., Makita N., Kimura T.
  • Organizer: The 40th Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research
• [Presentation] Modeling Overlapping Phenotypes of Long-QT and Brugada Syndrome with CACNA1C-E1115K that Alters Ion Selectivity of the Cardiac L-Type Calcium Channel Using Induced Pluripotent Stem Cells (2019)
  • Author(s): Kashiwa A., Makiyama T., Kohjitani H., Hirose S., Gao J., Kashiwa A., Huang H., Ishikawa T., Ohno S., Chonabayashi K., Suda K., Yoshida Y., Horie M., Makita N., Kimura T.
  • Organizer: 第66回日本不整脈心電学会
• [Presentation] Functional Reappraisal of SCN5A Mutations Reemphasize Their Predictive Value for Lethal Cardiac Events in Brugada Syndrome (2019)
  • Author(s): Ishikawa T., Makita N.
  • Organizer: 第66回日本不整脈心電学会
• [Presentation] Cardiac Emerinopathy, Novel Nonsyndromic Xlinked Left Ventricular Noncompaction Associated With Progressive Atrial Conduction Disturbance (2019)
  • Author(s): Ishikawa T., Barc J., Mishima H., Hirono K., Terada S., Kowase S., Sato T., Mukai Y., Yui Y., Ohkubo K., Kimoto H., Hata Y., Aiba T., Ohno S., Chishaki A., Shimizu W., Horie M., Ichida F., Nogami A., Yoshiura K., Schott JJ., Makita N.
  • Organizer: The 40th Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research
• [Presentation] 患者由来iPS 細胞モデルを用いたCav 1.2イオン選択性を障害するCACNA1C-E1115K変異がQT 延長症候群、Brugada 症候群を発症するメカニズムの解析 (2019)
  • Author(s): 柏麻美, 牧山武, 糀谷泰, マウリッセン トーマス, ウリヤンハイ イミン, 山本雄大, ガオ ジンシャン, ファン ハイ, 今村知彦, 相澤卓範, 石川泰輔, 大野聖子, 豊田太, 佐藤誠一, 高橋一浩, ウォルツェン クヌート, 堀江稔, 蒔田直昌, 木村剛
  • Organizer: 第97回日本生理学会大会
• [Presentation] 進行性心臓伝導障害患者の網羅的遺伝子解析とin vitro 機能解析系を用いて明らかになった心臓コネキシン病の分子病態 (2019)
  • Author(s): 石川泰輔, 関明子, 蒔田直昌
  • Organizer: 第97回日本生理学会大会
• [Presentation] Brugada症候群の予後予測に対する分子生理学的アプローチ (2019)
  • Author(s): 石川泰輔, 蒔田直昌
  • Organizer: 第67回日本心臓病学会学術集会
• [Presentation] 発症前診断を行ったQT延長症候群の姉妹 (2019)
  • Author(s): 松下悠紀, 永田弾尺, 小川昌宣, 鹿田佐和子, 石川泰輔, 蒔田直昌
  • Organizer: 日本人類遺伝学会第64回大会
• [Presentation] 次世代シーケンス解析による特発性心室細動の遺伝背景の解明 (2019)
  • Author(s): 謝颯琴, 高橋篤, 大野聖子, 鎌倉令, 石川泰輔, 植田初江, 斯波真理子, 南野直人, 林研至, 八木原伸江, 中野由紀子, 伊藤英樹, 宮本恵宏, 田中敏博, 蒔田直昌, 堀江稔, 清水渉, 草野研吾, 安田聡, 相庭武司
  • Organizer: 日本人類遺伝学会第64回大会
• [Presentation] 若年発症の家族性心房細動症例で遺伝子異常を認めた1例 (2019)
  • Author(s): 岩橋英明, 熊埜御堂淳, 高橋淳彌, 大渕綾, 本多亮博, 平方佐季, 大塚昌紀, 大江征嗣, 蒔田直昌, 福本義弘
  • Organizer: 日本内科学会 第326回九州地方会
• [Presentation] 不整脈症候群で心臓が構造的に正常な患者における心筋症の原因遺伝子変異の特定 (2018)
  • Author(s): 八木原伸江, 渡部裕, 蒔田直昌, 堀江稔, 清水渉, 大野聖子, 長谷川奏恵, 相庭武司, 田中敏博, 角田達彦, 重水大智, 徹 南野
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] CaMKII as a target for novel therapy to treat lethal ventricular tachyarrhythmias. (2018)
  • Author(s): 辻幸臣, 蒔田直昌
  • Organizer: 第57回日本生体医工学学会大会
• [Presentation] CALM2関連性QT延長症候群iPSCモデルにおいて、l-cis-diltiazemは遅延したL型calciumチャネルの不活性化をさらに強める (2018)
  • Author(s): 横井文香, 牧山武, 山本雄大, 張田健志, Yimin Wuriyanghai, 早野護, 西内英, 糀谷泰彦, 廣瀬紗也子, 高景山, 大野聖子, 豊田太, 吉田善紀, 蒔田直昌, 堀江稔, 木村剛
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Torsadogenic Action Of Late Na+ Current In Experimental Electrical Storm (2018)
  • Author(s): Yamazaki M., Tsuji Y. , Niwa R., Tomii N., Arafune T., Honjo H., Dobrev D., Nattel S., Kodama I., Sakuma I., Makita N.
  • Organizer: The 39th Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research / Invited
• [Presentation] Single Cell Electrophysiological Analysis of Human iPS Cell-Derived Cardiomyocytes Generated from Long-QT Syndrome Patients Carrying a CALM2 Mutation Using a Membrane Voltage Imaging System (2018)
  • Author(s): Yamamoto Y., Makiyama T, Wuriyanghai Y., Kohjitani H., Hirose S., Gao J, Kashiwa A., Kimura T., Ishikawa T., Motomura H., Makita N, Ohno S., Chonabayashi K., Yoshida Y., Suda K., Horie M
  • Organizer: The 11th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research / Invited
• [Presentation] The inactivation of L-type Ca2+ Channel was impaired in Human iPS Cell Model of Long-QT Syndrome with CALM2-D134H Mutation. (2018)
  • Author(s): Yamamoto Y., Makiyama T., Harita T., Hayano M., Nishiuchi S., Wuriyanghai Y., Kohjitani H., Hirose S., Yokoi F., Ishikawa T., Ohno S., Chonabayashi K., Suda K., Yoshida Y., Horie M., Makita N., Kimura T.
  • Organizer: 第82回日本循環器学会学術集会
• [Presentation] Duration Predicts Events In Caucasians With E1784K-SCN5A: The E1784K International Consortium (2018)
  • Author(s): Wijeyeratne Y. ,Makita N. et al
  • Organizer: The 39th Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research / Invited
• [Presentation] Mechanisms of Electrical Storm Associated With QT Prolongation: Successful Mapping of Torsades de Pointes in Rabbits (2018)
  • Author(s): Tsuji Y., Yamazaki M., Niwa R., Tomii N., Arafune T., Honjo H., Dobrev D., Nattel S., Kodama I., Sakuma I., Makita N
  • Organizer: American Heart Association Annual Scientific Sessions 2018
  • Int'l Joint Research / Invited
• [Presentation] HCN4 Polymorphisms and Tachycardia Induced Cardiomyopathy (2018)
  • Author(s): Nakano Y., Ochi H., Onohara Y., Sairaku A., Tokuyama T., Motoda C., Matsumura H., Tomomori S., Amioka M., Hironobe N., Ohkubo Y., Okamura S., Makita N., Yoshida Y., Chayama K., Kihara Y.
  • Organizer: The 65th Annual Meeting of the Japan Heart Rhythm Society
• [Presentation] Clinical Manifestations and Long-term Mortality in Lamin A/C Mutation Carriers from the Japanese Multicenter Registry (2018)
  • Author(s): Nakajima K., Aiba T., Makiyama T., Nishiuchi S., Ohno S., Doi T., Shizuta S., Onoue K., Yagihara N., Ishikawa T., Watanabe I., Oginosawa Y., Nogami A., Aonuma K., Saitoh Y., Kimura T., Makita N., Shimizu W., Horie M., Kusano K.
  • Organizer: The 65th Annual Meeting of the Japan Heart Rhythm Society
• [Presentation] Genotype-Dependent Differences in Short QT Syndrome (2018)
  • Author(s): Makita N.
  • Organizer: The 11th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research / Invited
• [Presentation] Atrial Conduction Defects Caused by a Connexin45 Mutation (2018)
  • Author(s): Makita N.
  • Organizer: The 11th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research / Invited
• [Presentation] Novel Arrhythmia Syndrome Associated with Gap Junction Mutations (2018)
  • Author(s): Makita N.
  • Organizer: The 11th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research / Invited
• [Presentation] Clinical and Genetic Basis of Calmodulinopathy (2018)
  • Author(s): Makita N.
  • Organizer: The 11th Asia Pacific Heart Rhythm Society Scientific Session
  • Int'l Joint Research / Invited
• [Presentation] Pathophysiology of Inherited Arrhythmias Associated with Ca Handling Abnormality (2018)
  • Author(s): Makita N.
  • Organizer: The 65th Annual Meeting of the Japan Heart Rhythm Society
• [Presentation] Mutation Hot-spot-based Risk Stratification In Long QT Syndrome Type 1: Data From A Nationwide Japanese LQT Registry (2018)
  • Author(s): Kashiwa A., Aiba T., Makimoto H., Yamagata K. , Keiko S. , Yagihara N., Watanabe H. , Ohno S., Hayashi K. , Sumitomo N., Yoshinaga M. , Morita H., Miyamoto Y. , Makita N. , Horie M., Yasuda S., Kusano K., Shimizu W. , The_Japanese_LQTS_registry_investigators.
  • Organizer: The 39th Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research / Invited
• [Presentation] Cardiac Connexin Syndrome: A New Inherited Cardiac Conduction Disease Entity with Distinct Electrophysiological and Extracardiac Manifestations. (2018)
  • Author(s): Ishikawa T., Seki A., Hagiwara N., Makita N.
  • Organizer: 第82回日本循環器学会学術大会
• [Presentation] Rare Coding Variants in Genes Other Than SCN5A Are Minimal Genetic Burden on the Prognosis of Brugada Syndrome (2018)
  • Author(s): Ishikawa T., Mishima H., Ohno S., T. Aiba, Nakano Y., Aizawa Y., Nakajima T., Hayashi K., Murakoshi N., Yagihara N., Kimoto H., Makiyama T., Watanabe H., Morita H., Yoshiura K., Nogami A., Shimizu W., Horie M., Tanaka T., Makita N.
  • Organizer: The 65th Annual Meeting of the Japan Heart Rhythm Society
• [Presentation] Lack Of Genotype-phenotype Correlation In Brugada Syndrome And Sudden Arrhythmic Death Syndrome Families With Reported Pathogenic SCN1B Variants (2018)
  • Author(s): Gray B. , Hasdemir C. , Ingles J. , Aiba T., Makita N. , PROBST V. , Wilde A., Semsarian C. , Sy R., Behr E.
  • Organizer: The 39th Heart Rhythm Society Scientific Sessions
  • Int'l Joint Research / Invited
• [Book] ゼロから学ぶブルガダ症候群 (2020)
  • Author(s): 石川泰輔, 蒔田直昌
  • Total Pages: 133
  • Publisher: 大道学館出版部
  • ISBN: 9784924391840
• [Book] 不整脈 識る・診る・治す (2018)
  • Author(s): 辻幸臣 蒔田直昌（平尾見三、小室一成編）
  • Total Pages: 376
  • Publisher: 中山書店
  • ISBN: 9784521745855
• [Book] 循環器科の心電図 (2018)
  • Author(s): 石川泰輔 蒔田直昌（村川 裕二編）
  • Total Pages: 224
  • Publisher: 南江堂
  • ISBN: 9784524237913
• [Remarks] 国立循環器病研究センター 創薬オミックス解析センター 研究プロジェクト
  • URL: http://www.ncvc.go.jp/omics/research/project03.html
• [Remarks] 国立循環器病研究センター創薬オミックス解析センター ホームページ
  • URL: http://www.ncvc.go.jp/omics/research/project05.html